RESUMO
Polymorphisms present in the TNF promoter region has shown to influence the gene transcription. Leprosy displays different clinical manifestations according to the immune responses of the individual infected with Mycobacterium leprae. In this study, we evaluated the single nucleotide polymorphisms (SNPs) -238 G/A (rs361525), -308 G/A (rs1800629), -857 C/T (rs1799724), -863 A/C (rs1800630) and -1031 T/C (rs1799964) in the promoter region of the TNF to see whether these SNPs influence host-susceptibility to leprosy and the different clinical manifestation. Nucleotide sequencing was performed with DNA samples from 108 leprosy patients and 253 control subjects. An association between -1031 C/C genotype and protection from leprosy was observed when leprosy patients were compared to controls (OR 0.11; 95% CI=0.01-0.82; p=0.012). The -857 C/T genotype may be associated with susceptibility to leprosy (OR=1.81; 95% CI=1.09-3.00; p=0.028). Similar genotype and allele frequencies for the SNPs -308 G/A and -238 G/A were observed between leprosy patients and control subjects. Altogether, TNF polymorphisms in the promoter region may be predictive of leprosy outcome.
Assuntos
Hanseníase/imunologia , Mycobacterium leprae/imunologia , Fator de Necrose Tumoral alfa/genética , Biomarcadores/metabolismo , Brasil , Análise Mutacional de DNA , Progressão da Doença , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Hanseníase/diagnóstico , Hanseníase/genética , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , Regiões Promotoras Genéticas/genéticaRESUMO
Leprosy displays a wide clinical spectrum that is dependent of the type of immune response. We investigate here whether polymorphisms in the promoter region of the IL12RB2 gene are associated with susceptibility or resistance to clinical forms of leprosy. Nucleotide sequencing of the promoter region of IL12RB2 encompassing SNPs -1035 A/G, -1033 T/C, -1023 A/G, -650 del/G and -464 A/G was performed on DNA samples from 105 leprosy patients and 108 healthy controls. However, none of the SNPs were associated with susceptibility to the disease or any of its clinical forms. Similarly, haplotype analysis did not show any association. The haplotype -1035A/-1033T/-650G/-464A was prevalent, and homozygosity for this haplotype was associated to a lower distribution of CD4(+) T cells (p=0.041). Our data suggest that polymorphisms present in the promoter region of IL12RB2 may not be associated with susceptibility to leprosy or its clinical forms.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Hanseníase/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Receptores de Interleucina-12/genética , Adolescente , Adulto , Idoso , Brasil , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/patologia , Estudos de Casos e Controles , Suscetibilidade a Doenças , Feminino , Frequência do Gene , Haplótipos , Homozigoto , Humanos , Hanseníase/imunologia , Hanseníase/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
Previous studies identified the variant IFNG +874A/T (rs2430561) in the first intron of the gene in association with mycobacterial infection, especially tuberculosis and leprosy. The aim of this investigation was to analyze the protective role of the T allele in relation to leprosy using a meta-analysis evaluation. Thus, 1573 patients and 1914 controls were included and analyzed in fixed effects model. The T allele is associated with a protective effect for leprosy under the dominant model (pooled OR=0.83, 95% CI=0.72-0.96, p=0.011) suggesting that carriers of the IFNG +874T allele may be protected from developing leprosy. The T allele has been suggested to correlate with high interferon-γ levels. A phenotype with high IFN-γ producing and an increased inflammatory profile may account for these findings. This meta-analysis suggests that IFNG +874T allele is associated with leprosy resistance.
Assuntos
Resistência à Doença/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Interferon gama/genética , Hanseníase/genética , Hanseníase/imunologia , Polimorfismo de Nucleotídeo Único/genética , Alelos , Heterogeneidade Genética , Humanos , Viés de PublicaçãoRESUMO
Polymorphisms present in the first intron of IFN-γ may have an important role in the regulation of the immune response, which could have functional consequences for gene transcription. Leprosy patients are characterized by different immune responses in different clinical forms. We investigated a possible association of the +874 polymorphism and CA repeats present in the first intron of IFN-γ with susceptibility to leprosy and with the manifestation of the different clinical forms. Nucleotide sequencing was performed with samples from 108 leprosy patients and 113 controls subjects, as well as immunophenotyping of CD(4)(+), CD(8)(+) and CD(69)(+) T cells by flow cytometry. The data showed that there were no significant differences between patients and control subjects, as well as according classification of Ridley-Jopling. However, the A/A genotype was significantly increased in paucibacillary patients (p=0.028) and the microsatellite encoding 16 CA repeats were significantly associated with paucibacillary compared to multibacillary patients (p=0.019). Individuals homozygous for the +874 A allele, the mean level of CD(4)(+) and CD(69)(+) T cells was higher. Our data suggest that polymorphisms present in the first intron of IFN-γ are not associated with susceptibility to leprosy, nevertheless, the +874 polymorphism and the CA repeats number encoded in IFN-γ gene may be related to a higher cellular immune response in patients and are consistently more frequently detected in PB patients.